ESPE Abstracts

Objective: To present the novel finding of hypergonadotropic hypogonadism, pubertal progress and molecular alterations in two sisters with variable phenotype.

Case Presentation: Two Greek sisters were investigated. The eldest was referred for investigation of short stature, at the age of 9 and 5/12 years. There was no positive family history for short stature. Physical examination revealed no dysmorphic features, and she was prepubertal according to Tanner staging. She was diagnosed with growth hormone deficiency (peak GH 6 ng/ml, IGF-I 148.7 ng/ml) and she continues on growth hormone replacement therapy with good response to treatment and normal height at present (10%ile). At the age of eleven years old she had breast development, however, laboratory investigation, revealed hypergonadotrophic hypogonadism, (FSH 31.24 m IU/ml LH 5.44 m IU/ml, estradiol 12.6 pg/ml). The karyotype was female 46, X, der (X) t (X; 20) (q21.32; p12.3). Her sister who, at the age of 10 years, was of normal height and prepubertal, was also investigated. She had elevated gonadotropins and the same karyotype as her sister. Ultrasound and magnetic resonance imaging of the uterus and ovaries in both sisters showed a similar picture. The right ovary was recognized with a cystic formation of 0.91 ml in the presence of an intact follicle, while on the left, fibrous tissue was recognized at the site of the left ovary (0.16 ml). In the younger sister the left ovary was not recognized. Array-CGH analysis detected a genomic pattern of female sex and the presence of: A) a size duplication ~ 8 megabases of the chromosomal region 20p13p12.3 (chr20: 60,747_8,117,942) that includes, according to the OMIM database 76 genes. B) a deletion ~ 61.5 megabases of the chromosomal region Χq21.33q28 (chrX: 93,622,826_155,226,073) which includes, according to the OMIM database, 102 genes. The older patient at the age of 12.5 years had menarche. The laboratory results at this age were FSH 35.86 mIU / ml, LH 59.95 mIU / ml, Estradiol 173.9 pg / ml, antimullerian hormone <0.01 ng/ml.